1. Field of the Invention
This invention relates to partially methylated cyclodextrins with enhanced solubility in water, and to a process for producing the same.
2. Description of the Prior Art
As known methylated products of cyclodextrin (hereinafter abbreviated as "CD"), there may be mentioned hexakis-(2,6-di-O-methyl)-.alpha.-CD, heptakis-(2,6-di-O-methyl)-.beta.-CD and heptakis-(2,3,6-tri-O-methyl)-.beta.-CD. Processes for producing these methylated CD's are also known, in which CD is methylated with dimethyl sulfate or methyl iodide in an organic solvent, such as N,N-dimethylformamide (hereinafter abbreviated as "DMF") and dimethyl sulfoxide (hereinafter abbreviated as "DMSO") in the presence of barium oxide and/or barium hydroxide, or methylated by 9 to 30 equivalent proportions, based on CD, of dimethyl sulfate in water in the presence of 15 to 40 equivalent proportions of sodium hydroxide (for example, Chemical Abstract, 98, p.108 (1983); Starch/Starke, 32, Nr. 5, pp.165-169 (1980)etc.).
CD is a group of cyclic oligosaccharides composed of several glucose units linked together through .alpha.-1,4 bond. These serve as host molecules to include various organic compounds, and have found use in pharmaceuticals, pesticides, perfumes, cosmetics, toiletries and other fields.
However, their low solubility in water and organic solvents, such as alcohol, has limited their widespread use in the above-mentioned applications. .beta.-CD (composed of seven glucose units), which is capable of including a wide variety of compounds, is particularly low in water solubility, and hence its service concentration is very limited.
The art-known methylated CD's mentioned above were prepared principally from an incentive to characterize the structure of CD's. As stated later, these methylated products, though somewhat enhanced in solubility in water, still suffer from the above-mentioned disadvantage because the solubility tends to lower with increasing temperature.
Noting that the lower solubility of CD's in various solvents compared with linear oligosaccharides of the same number of glucose units is due to their peculiar molecular structure, we attempted to break away from the symmetric molecular structure of the art-known methylated CD's by preparing partially methylated CD's. This study led us to find that the above-mentioned problems can be solved by properly controlling the methylation degree at 3-hydroxyl groups in glucose units. The first part of this invention is based on these findings.
Thus this invention provides partially methylated CD's wherein the average degree of methylation at hydroxyl groups of different positions is about 53 to 64% for the 2-position about 38 to 51% for the 3-position and about 70 to 100% for the 6-position, when measured by gas chromatography analysis. More specifically, this invention provides partially methylated CD's represented by the following general formula ##STR1## (wherein n is an integer from 6 to 8, and R expresses a hydrogen atom and/or methyl group), in which about two (on average) 3-hydroxyl groups in the molecule are methylated, and in which the 2- and 6-hydroxyl groups, which are far higher in reactivity than the 3-hydroxyl groups, are more completely methylated. The partially methylated CD as defined above may exist as a mixture of one compound in which a pair of glucose units with methylated 3-hydroxyl groups are adjacent to each other, with another compound in which these two glucose units are apart from each other across one or two glucose residues.
The second part of this invention is concerned with a process for efficiently producing the partially methylated CD's described above. More particularly it relates to a process for producing the partially methylated CD's as defined above by reaction of a CD with dimethyl sulfate, wherein more than about 30 equivalent proportions, based on CD, of dimethyl sulfate and more than about 30 equivalent proportions of an alkali metal hydroxide are used, and wherein the concentration of reactants is kept higher than 10% (wt/wt).